IntroductionWe describe temporal trends in the mortality rates and factors associated with AIDS and non-AIDS related mortality at the Evandro Chagas Clinical Research Institute (IPEC), Oswaldo Cruz Foundation (FIOCRUZ).MethodsAdult patients enrolling from 1986 through 2009 with a minimum follow up of 60 days were included. Vital status was exhaustively checked using patients’ medical charts, through active contact with individuals and family members and by linkage with the Rio de Janeiro Mortality database using a previously validated algorithm. The CoDe protocol was used to establish the cause of death. Extended Cox proportional hazards models were used for multivariate modeling.ResultsA total of 3530 individuals met the inclusion criteria, out of which 868 (24.6%) deceased; median follow up per patient was 3.9 years (interquartile range 1.7–9.2 years). The dramatic decrease in the overall mortality rates was driven by AIDS-related causes that decreased from 9.19 deaths/100PYs n 1986–1991 to 1.35/100PYs in 2007–2009. Non-AIDS related mortality rates remained stable overtime, at around 1 death/100PYs. Immunodeficiency significantly increased the hazard of both AIDS-related and non-AIDS-related causes of death, while HAART use was strongly associated with a lower hazard of death from either cause.ConclusionsOur results confirm the remarkable decrease in AIDS-related mortality as the HIV epidemic evolved and alerts to the conditions not traditionally related to HIV/AIDS which are now becoming more frequent, needing careful monitoring.

Studies on the long-term safety and tolerability of HAART are scarce in developing countries. HAART has been universally available in Brazil since 1997, providing a unique opportunity to evaluate the incidence and risk factors for HAART discontinuation or modification. We analyzed retrospective data from 670 treatment-naive patients followed at the HIV cohort of Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation, in Rio de Janeiro, Brazil, who first received HAART between January 1996 and December 2006. Our four outcomes of interest were treatment failure (TF-MOD), short-term toxicity (ST-MOD), long-term toxicity (LT-MOD), and overall modification/discontinuation (MOD, composed of TF-MOD, ST-MOD, LT-MOD, and other reasons). Risk factors were assessed using Cox's proportional hazards regression. Incidences of MOD, ST-MOD, LT-MOD, and TF-MOD were 28.3, 24.0, 4.0, and 5.6 per 100 persons-years, respectively. MOD was observed in 69% of the patients; 40% of the MODs were toxicity related. The risk of MOD in the first year of treatment was 32% (95% CI: 28.3-35.5%); the median time from HAART initiation to MOD was 14 months (IQR: 3.0-29.5). The most frequent reasons for ST-MOD were gastrointestinal; women had a higher hazard for ST-MOD. Metabolic toxicity was the most frequent reason for LT- MOD, particularly dislipidemia and lipodystrophy. Increased hazard of TF-MOD was observed among those with lower CD4(+) lymphocyte counts (<200 cells/mm(3)). Our results indicate that toxicities can compromise adherence and thus impact future treatment options. This is especially relevant in the context of limited access to second and third line treatment regimens.

BackgroundTuberculosis is the most frequent opportunistic infection and the leading cause of death among persons living with HIV in several low and middle-income countries. Mortality rates during tuberculosis treatment and death causes among HIV-1/TB co-infected patients may differ based on the immunosuppression severity, timing of diagnosis and prompt initiation of tuberculosis and antiretroviral therapy.MethodsThis was a retrospective observational study conducted in the clinical cohort of patients with HIV-1/Aids of the National Institute of Infectious Diseases Evandro Chagas, Rio de Janeiro, Brazil. All HIV-1 infected patients who started combination antiretroviral therapy up to 30 days before or within 180 days after the start of tuberculosis treatment from 2000 to 2010 were eligible. Causes of death were categorized according to the "Coding Causes of Death in HIV” (CoDe) protocol. The Cox model was used to estimate the hazard ratio (HR) of selected mortality variables.ResultsA total of 310 patients were included. Sixty-four patients died during the study period. Mortality rate following tuberculosis treatment initiation was 44 per 100 person-years within the first 30 days, 28.1 per 100 person-years within 31 and 90 days, 6 per 100 person-years within 91 and 365 days and 1.6 per 100 person-years after 365 days. Death probability within one year from tuberculosis treatment initiation was approximately 13%. In the adjusted analysis the associated factors with mortality were: CD4 ≤ 50 cells/mm3 (HR: 3.10; 95% CI: 1.720 to 5.580; p = 0.00); mechanical ventilation (HR: 2.81; 95% CI: 1.170 to 6.760; p = 0.02); and disseminated tuberculosis (HR: 3.70; 95% CI: 1.290 to 10.590, p = 0.01). Invasive bacterial disease was the main immediate cause of death (46.9%).ConclusionOur results evidence the high morbidity and mortality among patients co-infected with HIV-1 and tuberculosis in Rio de Janeiro, Brazil. During the first year following tuberculosis diagnosis, mortality was the highest within the first 3 months, being invasive bacterial infection the major cause of death. In order to successfully intervene in this scenario, it is utterly necessary to address the social determinants of health contributing to the inequitable health care access faced by this population.

IntroductionPeople living with HIV (PLHIV) on antiretroviral therapy (ART) experience high rates of non‐communicable diseases (NCDs). These co‐morbidities often accumulate and older adults may suffer from multimorbidity. Multimorbidity has been associated with loss of quality of life, polypharmacy, and increased risk of frailty and mortality. Little is known of the trends or predictors NCD multimorbidity in PLHIV in low‐ and middle‐income countries.MethodsWe examined NCD multimorbidity in adult PLHIV initiating ART between 2003 and 2014 using a multi‐site, observational cohort in Brazil. NCDs included cardiovascular artery disease, hyperlipidemia (HLD), diabetes, chronic kidney disease, cirrhosis, osteoporosis, osteonecrosis, venous thromboembolism and non‐AIDS‐defining cancers. Multimorbidity was defined as the incident accumulation of two or more unique NCDs. We used Poisson regression to examine trends and Cox proportional hazard models to examine predictors of multimorbidity.ResultsOf the 6206 adults, 332 (5%) developed multimorbidity during the study period. Parallel to the ageing of the cohort, the prevalence of multimorbidity rose from 3% to 11% during the study period. Older age, female sex (adjusted hazard ratio (aHR) = 1.30 (95% confidence interval (CI) 1.03 to 1.65)) and low CD4 nadir (<100 vs. ≥200 cells/mm3 aHR = 1.52 (95% CI: 1.15 to 2.01)) at cohort entry were significantly associated with increased risk of multimorbidity. Among patients with incident multimorbidity, the most common NCDs were HLD and diabetes; however, osteoporosis was also frequent in women (16 vs. 35% of men and women with multimorbidity respectively).ConclusionsAmong adult PLHIV in Brazil, NCD multimorbidity increased from 2003 to 2014. Females and adults with low CD4 nadir were at increased risk in adjusted analyses. Further studies examining prevention, screening and management of NCDs in PLHIV in low‐ and middle‐income countries are needed.

Background Mortality among HIV-infected individuals may differ by sex and mode of HIV acquisition. We studied mortality among women, heterosexual men, and men who have sex with men (MSM) in a cohort from Rio de Janeiro, Brazil. Methods HIV-infected adults followed at Instituto Nacional de Infectologia Evandro Chagas from 2000–2011 were included. Cox proportional hazards models accounting for competing risks were used to explore risk factors for AIDS and non-AIDS related deaths. Findings 2224 individuals were included (36·7%[817/2224] women, 24·9%[554/2224] heterosexual men, and 38·4%[853/2224] MSM). Throughout the study period, 103 deaths occurred: 64 due to AIDS-related causes, 31 due to non-AIDS related causes and 8 of unknown causes. In unadjusted analyses, compared to women, hazard of AIDS-related deaths was higher for heterosexual men (hazard ratio [HR] 3·52, 95% confidence interval [95%CI] 1·30–9·08) and for MSM (HR 2·30, 95%CI 0·89–5·94). After adjusting for confounders, excess risk of AIDS-related death observed for heterosexual men was attenuated (aHR 1·99, 95%CI 0·75–5·25, p-value=0.163), but unchanged for MSM (aHR 2·24, 95%CI 0·82–6·11, p-value=0.114). Non-AIDS related mortality did not differ by group. Interpretation Compared to women, increased risk of AIDS-related death among heterosexual men was partially mitigated by risk factors for AIDS mortality while excess risk observed among MSM was unchanged. Further study of reasons for AIDS-related mortality disparity by mode of transmission is needed.

Survival observed in this reference centre is comparable or longer than other international studies, although the choice of case definition criterion influenced findings. Adoption of the Ministry of Health case definition may enhance the ability to track the use of and outcomes from ART among AIDS patients.

Background The 30-day readmission rate is an indicator of the quality of hospital care and transition to the outpatient setting. Recent studies suggest HIV infection might increase the risk of readmission though estimates of 30-day readmission rates are unavailable among HIV infected individuals living in middle/low income settings. Additionally, factors that may increase readmission risk in HIV infected populations are poorly understood. Methods 30-day readmission rates were estimated for HIV-infected adults from the Instituto Nacional de Infectologia Evandro Chagas/Fiocruz cohort in Rio de Janeiro, Brazil, from January 2007 to December 2013. Cox regression models were used to evaluate factors associated with the risk of 30-day readmission. Results Between January 2007 and December 2013, 3991 patients were followed and 1861 hospitalizations were observed. The estimated 30-day readmission rate was 14% (95% confidence interval 12.3%–15.9%). Attending a medical visit within 30 days after discharge (aHR 0.73, p=0.048) and being hospitalized in more recent calendar years (aHR 0.89, p=0.002) reduced the risk of 30-day readmission. In contrast, low CD4 counts (51–200 cells/mm3: aHR 1.70, p=0.024 and ≤ 50 cells/mm3: aHR 2.05, p=0.003), time since HIV infection diagnosis ≥10 years (aHR 1.58, p=0.058) and leaving hospital against medical advice (aHR 2.67, p=0.004) increased the risk of 30-day readmission. Conclusions Patients with advanced HIV/AIDS are most at risk of readmission and should be targeted with prevention strategies to reduce this risk. Efforts to reduce discharge against medical advice and to promote early post-discharge medical visit would likely reduce 30-day readmission rates in our population.

BackgroundIn high-income settings, the spectrum of morbidity and mortality experienced by Human Immunodeficiency Virus (HIV)-infected individuals receiving combination antiretroviral therapy (cART) has switched from predominantly AIDS-related to non-AIDS-related conditions. In the context of universal access to care, we evaluated whether that shift would apply in Brazil, a middle-income country with universal access to treatment, as compared to France.MethodsTwo hospital-based cohorts of HIV-infected individuals were used for this analysis: the ANRS CO3 Aquitaine Cohort in South Western France and the Evandro Chagas Research Institute (IPEC) Cohort of the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. Severe morbid events (AIDS- and non-AIDS-related) were defined as all clinical diagnoses associated with a hospitalization of ≥48 hours. Trends in the incidence rate of events and their determinants were estimated while adjusting for within-subject correlation using generalized estimating equations models with an auto-regressive correlation structure and robust standard errors.ResultBetween January 2000 and December 2008, 7812 adult patients were followed for a total of 41,668 person-years (PY) of follow-up. Throughout the study period, 90% of the patients were treated with cART. The annual incidence rate of AIDS and non-AIDS events, and of deaths significantly decreased over the years, from 6.2, 21.1, and 1.9 AIDS, non-AIDS events, and deaths per 100 PY in 2000 to 4.3, 14.9, and 1.5/100 PY in 2008. The annual incidence rates of non-AIDS events surpassed that of AIDS-events during the entire study period. High CD4 cell counts were associated with a lower incidence rate of AIDS and non-AIDS events as well as with lower rates of specific non-AIDS events, such as bacterial, hepatic, viral, neurological, and cardiovascular conditions. Adjusted analysis showed that severe morbidity was associated with lower CD4 counts and higher plasma HIV RNAs but not with setting (IPEC versus Aquitaine).ConclusionsAs information on severe morbidities for HIV-infected patients remain scarce, data on hospitalizations are valuable to identify priorities for case management and to improve the quality of life of patients with a chronic disease requiring life-long treatment. Immune restoration is highly effective in reducing AIDS and non-AIDS severe morbid events irrespective of the setting.